Abstract The present study aimed to examine the expression of hyperuricemia (HUA)-related factors in the body fluids of HUA patients and in renal tissues and body fluids of HUA mice to elucidate the underlying mechanism of HUA and provide theoretical basis for the diagnosis, prevention and treatment of this disease. A total of 51 HUA patients (HUA group), and 36 healthy subjects (control group) were included in the present study. The peripheral blood and urine were collected from all patients and healthy subjects. A total of 20 male Kunming mice were used to construct HUA model, and another 20 mice were used as controls. The kidney tissues, peripheral blood and urine were collected from all mice. ELISA was performed to determine the levels of interleukin-6 receptor (IL-6R) proteins in the serum and urine of human or mice, while western blotting was employed to determine the protein expression in the kidney tissues of mice. Quantitative real-time polymerase chain reaction was used to measure the expression of mRNA and miR-30b in all sample types. Dual luciferase reporter assay was performed to identify the direct interaction between 3′-untranslated region of IL-6R mRNA and miR-30b. The expression of IL-6R mRNA and protein was increased in serum and urine of HUA patients, while the expression of miR-30b was reduced in HUA patients when compared with healthy subjects. The contents of uric acid, urea nitrogen and creatinine in the blood of HUA mice model were significantly elevated. Similarly, the expression of IL-6R mRNA and protein was increased in kidney, serum and urine of HUA mice model, while the expression of miR-30b was reduced in kidney tissues, serum and urine of HUA mice model. Dual luciferase reporter assay showed that miR-30b was able to bind with 3′-UTR seed region of IL-6R mRNA to regulate its expression. These findings demonstrated that the expression of IL-6R in patients and mouse with HUA is elevated, which is related with the down-regulation of miR-30b. Therefore, miR-30b might participate in the pathological process of HUA by regulating IL-6R.

中文翻译：

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MicroRNA-30b通过调节白细胞介素6受体参与高尿酸血症的病理过程

摘要 本研究旨在检测 HUA 患者体液和 HUA 小鼠肾组织和体液中高尿酸血症（HUA）相关因子的表达情况，阐明 HUA 的潜在机制，为诊断、预防提供理论依据。和治疗这种疾病。本研究共纳入 51 名 HUA 患者（HUA 组）和 36 名健康受试者（对照组）。收集所有患者和健康受试者的外周血和尿液。共20只雄性昆明小鼠用于构建HUA模型，另外20只小鼠作为对照。收集所有小鼠的肾组织、外周血和尿液。进行ELISA以确定人或小鼠血清和尿液中白细胞介素6受体（IL-6R）蛋白的水平，而采用蛋白质印迹法测定小鼠肾组织中的蛋白质表达。定量实时聚合酶链反应用于测量所有样品类型中 mRNA 和 miR-30b 的表达。进行双荧光素酶报告基因测定以鉴定 IL-6R mRNA 的 3'-非翻译区与 miR-30b 之间的直接相互作用。与健康受试者相比，HUA 患者血清和尿液中 IL-6R mRNA 和蛋白质的表达增加，而 HUA 患者中 miR-30b 的表达降低。HUA小鼠模型血液中尿酸、尿素氮、肌酐含量显着升高。同样，IL-6R mRNA和蛋白在HUA小鼠模型肾脏、血清和尿液中的表达增加，而miR-30b在肾脏组织中的表达减少，HUA 小鼠模型的血清和尿液。双荧光素酶报告基因检测表明 miR-30b 能够与 IL-6R mRNA 的 3'-UTR 种子区结合以调节其表达。这些发现表明， HUA 患者和小鼠体内 IL-6R 的表达升高，这与 miR-30b 的下调有关。因此，miR-30b可能通过调节IL-6R参与HUA的病理过程。